Can we understand the mechanisms by which the gut microbiome contributes to digestion and health in infants? If so can we use this to accelerate this knowledge toward personalised microbiome-based nutrition concepts and novel food products for optimised health and wellbeing? In this episode Professor Tom Gilbert and editor Christina Lehmkuhl Noer talk to Henrik Munch Roager who is an Associate Professor and group leader of the Nutrition, Microbiome & Metabolomics research group at Department of Nutrition, Exercise and Sports, University of Copenhagen.
Your hosts are PhD Christina Lehmkuhl Noer and Professor Tom Gilbert. Sound and recording by Christian Grimes Schmidt from Centre for Online and Blended Learning and editing by Christina Lehmkuhl Noer and Ella Zoe Lattenkamp.
The Center for Evolutionary Hologenomics and this podcast are generously funded by the Danish National Research Foundation.
00:00:00 Henrik Roager
Children, they encounter a lot of their bacteria and microorganisms through their gastrointestinal system, and that's very important for educating the children's immune system. It's actually quite important what kind of microbiome you get and establish through the first years of life, because that's what you're stuck with.
00:00:21 Tom Gilbert
Welcome to another episode of Microbial Connections, a podcast where together with experts, we explore the essential connections that all life share with microbes. My name is Tom Gilbert.
00:00:33 Christina Lehmkuhl Noer
And I'm Christina Noer and we both work at Center for Evolutionary Hologenomics at University of Copenhagen.
00:00:40 Christina Lehmkuhl Noer
In this episode, we will talk to Associate Professor Henrik Roager who is looking into how the gut microbiome influence digestion and health in humans?
00:00:52 Christina Lehmkuhl Noer
But before we dive into your research, Tom and I always ask our guests to bring something that represents their research, and you were very fast at telling us what you would bring. So please let us know what did you bring?
00:01:08 Henrik Roager
I brought a diaper, and I did that because that's really an essential tool in our research to collect stool samples and urine samples from infants to study their microbes and the role of the microbes in early life.
00:01:24 Tom Gilbert
And why is it you care about the microbes in early life? Is that just so we have happy babies or is there a bigger connection?
00:01:28 Henrik Roager
So all we know that microbes are really essential for our digestion and health. We know that, yeah. Or their research throughout the last maybe 20 years.
00:01:40 Henrik Roager
And you can say that the establishment of these microbes happens in early life. So it's really important what goes on. There are not only for the children's development, but also for setting the stage for health later in life.
00:01:55 Christina Lehmkuhl Noer
Very cool. OK, but so the diaper here, it represents a way of measuring digestion in infants. But how exactly do you measure it? Do you examine the diapers or what do you do?
00:02:07 Henrik Roager
Yeah, so we've so fortunate to have parents that volunteer to help us do our research, and they do that by volunteering to collect samples from their newborn child.
00:02:20 Henrik Roager
From birth until one year rates. So basically we ask parents to collect samples every second week throughout the year, and the whole idea is basically that they will allow us to study their development of their children's gut microbes, how they develop and take form during their early life in.
00:02:41 Tom Gilbert
So by samples you mean you sample black gold?
00:02:43 Henrik Roager
Yeah. Poop samples. Yes, it's dirty samples. But parents have a very relaxed attitude to these samples, so it works out quite easy because parents are used to handle these samples anyway.
00:02:59 Tom Gilbert
I'm quite surprised you need nappies to do that, because when I had little kids, I used to wipe it of my face all the time and so anyway.
00:03:03 Christina Lehmkuhl Noer
So that's that.
00:03:07 Tom Gilbert
Yes.
00:03:07 Christina Lehmkuhl Noer
But so, why is it so important to understand this connection between the gut bacteria and the infants digestive health?
00:03:18 Henrik Roager
So, so maybe a surprising fact is basically that the way that children meet the the world is to a large extent through their GI tract, the gastrointestinal system, because the surface area in their GI tract is much bigger than the surface area of the skin of the child.
00:03:38 Henrik Roager
So children, they encounter a lot of their bacteria and microorganisms through their GI tract, and that's very that's very important for.
00:03:49 Henrik Roager
Educating the children's immune system. They have to recognise what is dangerous, what is not dangerous and basically yeah, encounter the world and that happens to a large extent through their GI system.
00:04:04 Christina Lehmkuhl Noer
So through what they eat and?
00:04:05 Henrik Roager
Yeah. For what they eat the dirt they get in their mouth. I mean, that is a way that they're training their immune system. You can say, yeah, so.
00:04:13 Tom Gilbert
I think it would be excellent to get into that further, but maybe just before let's go back to the diapers. So I mean you, you give the diapers to the parents. They collect these is that it? Or is there a more subtlety to your great poo master plan?
00:04:28 Henrik Roager
Yeah. So parents collect the fecal samples and then at the same time we ask the parents to record their infant nutrition, their dietary habits-based patterns. So whether the child is being breastfed, receive formula feeding or and later also when they get the contrary material diet, we ask their parents to record what kind of foods are they getting.
00:04:52 Henrik Roager
How much and the whole idea is. Or the reason for that is that we know that early life nutrition is super important and critical for the development of the microbes.
00:05:02 Tom Gilbert
So you're measuring what they're taking in what's coming out, but are there other factors? Are you measuring for example, can you measure, for example, how long it takes? And is that ravant?
00:05:11 Henrik Roager
Yeah. So we also very interested in understanding bowel habits. So basically, why do some children have a diaper, let's say 7 days, seven times a day, whereas others have 1:00 every second week?
00:05:26 Henrik Roager
And if you ask a doctor, he will say that's perfectly normal. It's no problem. And yes, we acknowledge it's not a problem per se, but we're just curious to understand why it has such huge variation in bowel habits and difficulties patterns in early life. And we know that in some cases.
00:05:45 Henrik Roager
If children have very few diapers per day, it actually comes with, sometimes with a lot of crying and difficulties in getting get rid of their poop for the children and also with some pain sometimes. So we know it can be really stressful not only for the child, but also for the parents.
00:06:03 Christina Lehmkuhl Noer
OK. And like so, why is it actually important to understand this connection between the gut bacteria and infants' digestive health? Like, how many infants experience these digestive problems?
00:06:15 Henrik Roager
Yeah. So if we think just in the Danish context, we know that around sixty thousand children are born each year and out of this, around 15% that are experiencing problems with infantile colic, diarrhea or constipation. So this is actually something that is quite common, especially within the first three to four months of life.
00:06:49 Henrik Roager
My interest in this also came when I when we got our first child. And she was born. And after two weeks, she started crying a lot, and already at that time I was doing my PhD in on got microbiology and microbes so I couldn't stop thinking about what is going on in her digestion, in her, in her gut, and later we could really see her stomach being very, very bloated so.
00:07:08 Henrik Roager
And there was also sometimes we could really sort of push out a lot of gas from her GI system. So we knew for sure that that was something causing her pain and it had to do with her digestion and that basically sparked my interest in this. So why are no one doing anything in this field and the doctors they say, well, it's just normal, it's not a problem and yes, there is no sort of health related issues, at least as we're aware of, but it's still come with a lot of distress and we would like to know about what is going on in in the in the gut of these infants.
00:07:48 Tom Gilbert
Yeah, I mean, I guess there's no health related issue for the baby, but there's a lot of mental anguish and issues for the parents, as you say, right? So. OK. But so coming back to the science.
00:07:59 Tom Gilbert
The babies have got these variable conditions, whether it's pooping Rayleigh or pooping frequently, and colic and so on. You think the microbes are involved. The microbes themselves, though, are shaped by the environment around there, right? So how do you think it all ties together? What is it you're exactly trying to study and and work out from it? And what will the solutions be that come from it?
00:08:19 Henrik Roager
That's some big questions. So so we think microbes could be partly involved in this, but there's probably a lot of other factors as well, but let's just focus on microbes. So microbes are shaped and formed by their nutrition, by their environment, whether the children have older siblings, whether there is pets in the in the.
00:08:44 Henrik Roager
Umm, how they erased it determines the exposure to microbes. So what we interesting is just trying to link how the microbes develop over time and how that relates to their nutrition and their environment that these children are raised in.
00:09:02 Henrik Roager
And then what we hope to do is to not only study the microbes but study their molecules that these microbes produce because we think that these microbes could be interacting with receptors, so functions in the gut that regulate gut motility. So peristaltic movements in the in the gut and that that could be a way by which microbes have an effect on gut Physiology and bowel habits basically.
00:09:32 Tom Gilbert
So how exactly do you do this? Your parents? I mean, you give them a diaper. What do you get back? What's the whole pipeline of going on from them? Taking a sample to it, getting to you to then the kind of data you generate, I'd just be interested to.
00:09:46 Henrik Roager
Hear what's going on there. Yeah. So, so parents, they collect stool samples at home, and they actually store them in their own freezer in very small containers.
00:09:56 Henrik Roager
And then on regular basis, they bring these samples, which has been frozen, they bring it to our lab, then we receive these samples and then they're sort of steps are to then later extract the DNA of these samples and then a sequence. So that means studying their their genomes of the bacteria.
00:10:16 Henrik Roager
To understand what are the microbes that are actually present there and in what abundance, are there there and how many are there and what are the diversity of the bacteria? And then in parallel, we also take, you can say faecal water. So there are water part of the faecal sample.
00:10:33 Henrik Roager
And then we extract molecules from this water with the aim of studying which molecules are present in the faeces, and we use something called liquor chromatography mass spectrometry, which are techniques that can measure the mass of molecules and that give us insights into which molecules are there and what concentration.
00:10:54 Henrik Roager
Saw there and together that gives us the opportunity to link their microbes, their molecules, to their children's style, but also to the bowel habit. So if we see that all the children that are constipated, they are dominated by a certain type of bacteria that seems to produce a certain molecule.
00:11:13 Henrik Roager
Well, that's then our hope is to to then take that knowledge and then go back to the lab and try mechanistically to sort out, OK can this molecule that this bacteria this bacteria produce, can it actually can actually.
00:11:28 Henrik Roager
Or peristalisis via certain interaction with certain receptors. So we start from the humans. The infants try to find patterns and then we work backwards to see if we can actually validate the mechanisms there. The patterns that we see.
00:11:43 Christina Lehmkuhl Noer
So like you already told us about like some of the factors that are influencing gut health in the babies, is that also happening very early in life like such as like how they are born or? Is their mom is able to breast feed them or?
00:12:01 Henrik Roager
Yes, sure. So once the children are born, their intestine is more or less sterile, so that also means that the microbes they encounter during and right after birth are their first microbes to colonise their intestine. So that means that it actually matters whether the child is born.
00:12:21 Henrik Roager
At a hospital where they spawn at home, or whether it's born by vaginal birth or C-section, it all has influences on which microbes get their first and how to.
00:12:33 Henrik Roager
Nice space.
00:12:35 Henrik Roager
So that's one thing. We also know that later in life then we cannot necessarily see these initial differences. So they are there for the first few months, but then they gradually disappear.
00:12:46 Tom Gilbert
So that's interesting because I mean, I know there's a lot of debate about how important it is that you're born through a natural birth versus caesarean. And I've heard people opine that if you are born through C-section and it's to sterile, it can have long lasting consequences. But is that a hypothesis or I mean there's no data for?
00:13:03 Henrik Roager
That or I think there are data suggesting that the risk of getting immune related diseases increases if you're born by C-section.
00:13:12 Henrik Roager
But, and that's probably due to the fact that their interactions between microbes and the immune system in the first few months of life are extremely important. So although you might not be able to see the differences in the microbial composition at one year of age between those that were born by 6 C-section and those that were vaginal.
00:13:31 Henrik Roager
The differences earlier in the first few months might still have been there and played an important.
00:13:35 Tom Gilbert
Role. OK, so this is this ties to the idea then that I think you mentioned at the very beginning that your gut microbes are somehow tuning your immune system because they're interacting with each other and kind of setting the way immune system develops.
00:13:46 Henrik Roager
Yes, yes, but actually another factor that can sort of play an important role in this is then also the mode of feeding, so we know that breast feeding.
00:13:57 Henrik Roager
Can compensate or overrule some of their effects of a C section birth. So, if a child is born by a C section, if that child is being breastfed afterwards, then it reverts more quickly back to the vaginal born or it mimics more than vaginal born child due to breastfeeding.
00:14:21 Tom Gilbert
So just to be clear to the list, I mean, the reason why you end up with different microbes is when you're vaginal born, you're going through the birth canal and you're literally imbibing being covered in microbes right from from that part of the body that you're not getting if you cut out the stomach, right?
00:14:27 Henrik Roager
Yeah. Yes.
00:14:35 Tom Gilbert
So breastfeeding can help address that. But are there other mechanisms that say you know a baby has to be born by C-section? Are there other ways the baby can be helped to?
00:14:45 Henrik Roager
I mean, there is currently being done experiments with testing. It's called vaginal seeding. So basically children that are born by C-section for one reason.
00:14:56 Henrik Roager
Then they are being vaginal seeded so they are actually getting microbes from their mothers vagina seeded on the skin and the mouth of the child right after birth. And the whole idea is that that maybe that can sort of help their child to get exposed to their microbes in a different way and.
00:15:18 Henrik Roager
And that has been done short term. So they know now or scientists know that yes that can correct or help the microbiom be more similar to a vaginal bone child. But the long-term consequences are not currently known but now new studies are currently being conducted with the aim of following the children over a longer period of time and see if it actually have an impact on the risk of developing allergies or asthma or eczema later in life.
00:15:47 Christina Lehmkuhl Noer
Yeah. Because speaking of those broader implications for the childhood, as they grow up, like how much do we know about that you were talking about immune system. And the other things that can be affected.
00:15:59 Henrik Roager
Yeah, so so for quite some time we have this have had this hygiene hypothesis. So the idea that if you are born at a farm or if you are born in a household with older siblings and pets then you are less likely to develop immune related diseases later in life.
00:16:22 Henrik Roager
And that comes back to you or and then the most recent ideas is then that it comes back to that children needs to be exposed to more different microbes to educate the immune system, and that is lacking.
00:16:36 Henrik Roager
If a child is being raised in a very sterile environment. Being vaginal born, not receiving microbes from siblings or pets and and not being. Simply, their immune system is not being trained properly enough.
00:16:52 Christina Lehmkuhl Noer
And is that the bacteria in the infant's gut that is actually communicated with the immune system or?
00:16:57 Henrik Roager
Yeah, that's what we think that it's of. Well, it's a, it's a micro organisms that enter the gut that needs to stimulate the immune system. Of course it does mean that we should feed our children dirt and whatever we find.
00:17:13 Henrik Roager
So it's not that hygiene is is not a good thing. It can be a definitely a good thing. We need to think about that actually we need exposure to our environment to educate our immune system in our life.
00:17:27 Tom Gilbert
So this raises actually, I guess an obvious question. Let's say it turns out there is a benefit of vaginal seating and so on. But yeah, we have all these people born from C sections that were too sterile in in the past.
00:17:38 Tom Gilbert
Is it too late? Are there solutions? Do you think? Do you think these people are condemned towards hyper allergic reactions? I mean, what are your thoughts on that I mean?
00:17:48 Henrik Roager
So I think first of all, it's important to say that just because you're born by C-section, it doesn't mean per SE that you'll get immune related diseases, but the risks are just high.
00:18:01 Henrik Roager
Secondly, I'm not so sure we can actually correct it. Of course it might. We might be more susceptible for developing certain diseases if we didn't get the right immune education when we were when we were young, but I think it's difficult to correct it per SE, because I think a lot of the programming is happening in early on. So I think it's about risk and susceptibility that is being affected and maybe we can affect that later in life in as we are at it's more important what? How a lifestyle is yeah, but that's speculations I think.
00:18:42 Tom Gilbert
Yeah, but I think it does raise a very good point. I mean, even if there was some kind of lost benefit when you were born by C-section, I mean, I guess is to your health. Is as great as the fact that you might eat processed foods all the time, and so on is a very important thing to balance.
00:18:58 Tom Gilbert
Yeah. OK. And Henrik, you, you actually mentioned the interesting idea that even if you're born through a Caesarean mother's breast milk can actually help see the microbiome, right. And I guess it's because it's the contact with the skin. And are there microbes in breast milk itself or?
00:19:13 Henrik Roager
Yeah, that's also being discussed quite a bit. I think most of the microbes that come via the breast milk comes by the skin. So it's actually not so much their present or lack of microbes and breast milk that are the key here.
00:19:29 Henrik Roager
Another presence of some carbohydrates in their breast milk that are called human milk or cacrites. So these are we think important for the development of the gut microbiome because these are carbohydrates that.
00:19:44 Henrik Roager
They're our own host enzymes, so digestive enzymes cannot degrade in the upper part of the GI tract, meaning that these carbohydrates they reach the colon where bacteria has enzymes that can degrade these carbohydrates.
00:20:00 Henrik Roager
And that means you have a lunch pack that you give to the child that has the purpose of promoting certain bacteria in early life, and these bacteria are called bifidobacteria, and we think these are important in early life and we think that because there is this very close connection to their presence of human milk oligosaccharides and breast milk and they typically dominate their breastfed child, up to 90% of the microbiome between 50 and 90%.
00:20:30 Henrik Roager
And that's very unusual in adults. You don't see that in adults, that there are one group bacteria dominating to such a large extent. So this is a quite unique thing for the for the infants.
00:20:41 Christina Lehmkuhl Noer
And they are important for the infants?
00:20:45 Henrik Roager
Yes.
00:20:45 Christina Lehmkuhl Noer
You think for the health or?
00:20:46 Henrik Roager
Yeah, so we think these bacteria that they produce molecules that can interact with the immune system and thereby regulate immune responses in early life.
00:20:57 Christina Lehmkuhl Noer
Wow, do you do you think they can be put into the the artificial milk then or just?
00:21:01 Henrik Roager
Yeah. So Yes, so quite recently companies have been developing and also manufacturing these human milk oligosaccharides. So they are now being introduced into the formula milk. So you can now Denmark by formula milk containing a few of these human milk, oligosaccharides.
00:21:24 Henrik Roager
But The thing is that in breast milk you may have up to 200 different human milk oligosaccharides, so different carbohydrate structures.
00:21:31 Henrik Roager
So of course, data shoots diversity in that that's difficult to mimic in an infinite formula. So there you would find right now between 1-2 up to five different humanocytes and they are mainly chosen based on being them being most abundant in breast milk.
00:21:50 Henrik Roager
But it will never represent the whole diversity that you find in breast milk. So companies are trying to mimic formal milk to make it look like breast milk, breast milk and and I think this.
00:22:02 Henrik Roager
Development of human organs saccharides is an important step in towards that and I think it's also important to say I'm.
00:22:10 Henrik Roager
I mean, in some ways in it, a very good alternative for women that for one reason or another, cannot or will not breastfeed, and it provides all their essential nutrients for their child, for them to go and develop. So they get the the majority of what they need. But of course, infant formula is never going to be 100% matching their breast milk.
00:22:33 Christina Lehmkuhl Noer
No, but so I'm curious about knowing so. How do you see the role of these gut bacteria and the gut microbiome in the children in the children as they grow and evolve?
00:22:44 Henrik Roager
So there's a lot of fluctuations in the microbes throughout the first year of life, but once the child gets around 2 years of age, then it starts to stabilise a little more, meaning that it looks a bit like the adult gut microbiome. So that means that once the microbium is established at the age of 3-4 years of age, then it's actually surprisingly stable throughout childhood and adulthood. So it means it's actually quite important what kind of microbiome you get and establish through the first years of life, because that's what you're stuck with.
00:23:22 Henrik Roager
And these microbes are important also, for as an adult, because, I mean, they help us extract energy from the fibres we eat. So there is a bacteria that are specialised in degrading older diatribe fibres that we get from vegetables and fruits and grains.
00:23:41 Henrik Roager
If we don't have microbes that can digest these, then we risk losing their quite a bit of the health benefits from eating yeah, fibrate diets basically.
00:23:52 Tom Gilbert
That raises the question, is it possible for people like you to analyse the microbial content of a faecal sample and say this is a good community or this looks like a problematic 1? Is there a way to sort of give it a thumbs up that it's a healthy 1 or is it so subjective by?
00:24:07 Tom Gilbert
That gets tricky. Yeah, so.
00:24:10 Henrik Roager
Get your microbiome profile by companies, but.
00:24:13 Henrik Roager
I would say that at this point in time, it's actually very difficult to say this person is more healthy than this person because it's so individual individualised, or microbiome. Having said that, I think we can probably see the very.
00:24:29 Henrik Roager
The person having inflammatory bowel disease or having very, very disruptive microbiom, yes, we can pinpoint that. But we cannot at this point in time, give dietary advice based on your microbiome.
00:24:44 Christina Lehmkuhl Noer
I'm also very curious to hear your thoughts about so I know, at least in Denmark, there's this trend right now that a lot of people are eating Professorens grønne grød. So it's like the doctors Green Porridge. So it's a lot of blended vegetables and fruits.
00:25:02 Christina Lehmkuhl Noer
And they I think people believe that that will give you a healthier gut microbiome. And again, like boost your health. Do you believe in that or?
00:25:13 Henrik Roager
So I think it's important to say that this green porridge has never been tested in a proper clinical trial.
00:25:21 Henrik Roager
So we cannot say for sure there is evidence supporting eating this part. Having said that, you can say the parts with the green parts, which is blending a lot of different vegetables and fruits.
00:25:33 Henrik Roager
It's trying to condense the whole message that is important to eat a very diet. A lot of plants.
00:25:40 Henrik Roager
And that is sort of being condensed into a parts that people that can then easily implement in their daily life and thereby try to boost their microbiome and and and gut health. So you can say that the message is so clear and easy to understand and people get a feeling. Yes. Now I'm doing something.
00:26:01 Henrik Roager
And that is so good, but for I cannot say anything about the evidence for this purge. But I I get the premise. The idea behind it, it's about increasing your intake of vegetables and fruits. That's the key message, no matter.
00:26:17 Christina Lehmkuhl Noer
I know you've also been looking into adult digestion and digestion and athletes and stuff, and I'm really curious to hear about like, what do you think are the perspectives of this research that you're doing?
00:26:28 Henrik Roager
Yeah. So you can say, because we have such a stable microbiom through adulthood, and it's actually quite difficult to modulate.
00:26:36 Henrik Roager
We think it's very interesting to understand how do we respond differently to the same kind of diet, for example, so we can for sure see that although we eat the same thing, we respond differently in terms of our digestion and how the microbes respond to.
00:26:53 Henrik Roager
And the whole idea is that if we could understand why we respond differently, then we could potentially in the future tailor diet to the individual to favour a certain.
00:27:05 Henrik Roager
Aspect or to alleviate certain symptoms, and I think everyone can relate to this by thinking about that everyone has certain vest. That creates a certain gas production in their own gut, right, so we.
00:27:19 Tom Gilbert
The famous Jerusalem Artichoke I believe.
00:27:22 Henrik Roager
Yeah, exactly. So we all have an experience that there are certain foods that causes some pain or gas in our gut that we feel is uncomfortable and that's basically comes down to their personalised response that we have certain foods that in interaction with our microbes give us certain response.
00:27:42 Henrik Roager
So thinking about that, the perspectives are that maybe we can improve health.
00:27:48 Henrik Roager
By leveraging their individual microbes that we carry around in combination with specific diets, for example, to improve our ability to, yeah, extract energy, but also boost the immune system and maybe even our mental health.
00:28:04 Christina Lehmkuhl Noer
But hey, like, tell us like, what is the next steps in your research? Because it's so fascinating what you're doing. So what are you looking into next?
00:28:12 Henrik Roager
So I think one of the things I'm really excited about is our new research this soon going to be shared is about where we measure the environment throughout the gast multisner tract. So we have measured pH. How it varies between individuals in the GI tract and what's quite remarkable is that.
00:28:33 Henrik Roager
That the pH is highly variable between people, so we assume that pH in the small intestine largest intestine is quite consistent among individuals, but it's actually quite variable and that could be a key to understanding.
00:28:51 Henrik Roager
Why we all carry around different microbes, and why our microbes respond differently to same kind of bad. Because the environment that these microbes are living in might be highly variable between individuals.
00:29:04 Tom Gilbert
Crazy.
00:29:06 Christina Lehmkuhl Noer
Will be interesting to follow.
00:29:08 Henrik Roager
Yes.
00:29:09 Tom Gilbert
Yeah. Well, thanks again for all your time, Henrik. It was super interesting. Are there any last wise words, you'd like the listeners to take away?
00:29:16 Henrik Roager
No, I don't know. Take care of your microbes they take of you.
00:29:20 Tom Gilbert
Very, very wise. Well, well, thank you. We look forward to seeing you with your research. Thank you.